Sequence analysis has become a useful tool for characterization of circulating rotavirus strains. Previous work in our laboratory identified areas of sequence in the gene encoding the rotavirus outer capsid protein VP7 that appear to be associated with VP7 serotype specificity. Thus, strains which fail to react with serotype-specific monoclonal antibodies in an ELISA or which do not grow well in tissue culture can be characterized with molecular techniques. Sequence analysis can also be used to examine antigenic variation at the genetic level. Circulating rotavirus strains from various rotavirus vaccine trials are being analyzed by sequence analysis to determine whether viral antigenic variation is a factor in vaccine failure. In addition, the complete nucleotide sequence of the gene 9 from two "subtypes" of VP7 serotype 4 was determined and compared. It was possible to distinguish subtypes at the nucleotide and amino acid level. Whether subtypes of a serotype are relevant to vaccine development is under investigation.